Human embryonic stem cells (ESC) defined by their ability to self-renew indefinitely and to give rise to all adult cell types, are potentially invaluable in the field of regenerative medicine. However, without detailed knowledge on how this cellular plasticity is regulated, their full potential remains to be harnessed. PRDM14 was shown to be essential for maintaining the human ESC state and also enhances the efficiency of reprogramming fibroblasts back to a pluripotent state. In this study, I dissected the mechanism in which PRDM14 safeguards and induce pluripotency. Importantly, PRDM14 was found to co-bind pluripotency associated genes with core ESC regulators and directly regulates the expression of OCT4 in human ESC. On the other hand, PRDM14 also binds many developmental genes across the genome and was found to interact with the polycomb repressive complex II (PRC2) and this interaction is important for PRDM14-mediated repressive activity in human ESC and iPSC reprogramming.